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Published online before print May 15, 2007
Eur Respir J 2007, doi:10.1183/09031936.00009407
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ORIGINAL ARTICLE

Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung fibrosis

Z.G. Fridlender 1*, P.Y. Cohen 1, O. Golan 1, S. Wallach-Dayan 1, R. Breuer 2

1 Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
2 Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; and Dept of Pathology, Boston University School of Medicine, Boston, Massachusetts

* To whom correspondence should be addressed. E-mail: fridlender{at}hadassah.org.il.


  Abstract

Epithelial cell injury and apoptosis are recognized as early features in idiopathic pulmonary fibrosis and bleomycin-induced fibrosis in mice. Telomerase is a known apoptosis-alleviating factor. We studied the role of telomerase during bleomycin-induced lung epithelial cell (LEC) apoptosis in vitro in a mouse LEC line, and in vivo in LECs isolated from bleomycin-treated mice.

We evaluated changes in mTERT mRNA levels and changes in telomerase activity with the TRAPeze detection kit, telomeric length with the TeloTTAGGG Telomere Length Kit, and LEC apoptosis with FACScan and DAPI stain.

Twenty-four hours after bleomycin treatment in vitro, there was a significant elevation in mTERT mRNA and a transient 41% increase in telomerase activity. At 72 hours, telomerase activity had fallen to 26% below levels in untreated cells. Reduction of telomerase activity over time, or by direct inhibition, significantly elevated LEC apoptosis. No change in average telomeric length was noted. In vivo, telomerase activity of LECs from bleomycin-treated mice increased at 7 and 14 days.

We conclude that telomerase activity may play a protective role from robust bleomycin-induced lung epithelial cell apoptosis. Moreover, stabilizing telomerase activity may decrease epithelial cell apoptosis and the resulting lung fibrosis.

Keywords:  Apoptosis, bleomycin, epithelial cells, fibrosis, lung, telomerase




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